JP-A 10-72434 discloses a 2,4-substituted aniline derivative of the formula:
wherein R1 represents alkyl, haloalkyl, alkoxy, or the like; R2 represents hydrogen atom, alkyl, haloalkyl, or the like; R3 represents alkyl, cycloalkyl, alkenyl, or the like; X represents oxygen, sulfur, NR5 or a single bond; Q represents an azole or the like, and a herbicide comprising it.
However, said derivative is not reported to possess hypoglycemic action and hypolipidemic action.
Peroxisome proliferator-activated receptor gamma (PPARγ), a member of the intranuclear hormone receptor superfamily, which is typically exemplified by steroid hormone receptors and thyroid hormone receptors, plays an important role as a master regulator in the differentiation of adipose cells with its expression induced in the very early stage of adipose cell differentiation. PPARγ forms a dimer with the retinoid X receptor (RXR) by binding to a ligand, and binds to a responsive site of the target gene in the nucleus to directly control (activate) transcription efficiency. In recent years, the possibility that 15-deoxy-Δ12.14 prostaglandin J2, a metabolite of prostaglandin D2, serves as an endogenous ligand for PPARγ, has been suggested, and it has been shown that a class of insulin resistance enhancers, typically exemplified by thiazolidinedione derivatives, possess ligand activity for PPARγ, and that its potency is proportional to its hypoglycemic action or adipose cell differentiation-promoting action [Cell, vol. 83, p. 803 (1995): the Journal of Biological Chemistry, vol. 270, p. 12953 (1995); Journal of Medicinal Chemistry, vol. 39, p. 655 (1996)]. Furthermore, in recent years, it has been shown that 1) PPAR γ is expressed in cultured cells of human liposarcoma origin, whose proliferation is ceased by the addition of a PPARγ ligand [Proceedings of the National Academy of Sciences of the United States of America, vol. 94, p. 237 (1997)], 2) nonsteroidal anti-inflammatory drugs, typically exemplified by indomethacin and fenoprofen, have PPARγ ligand activity [the Journal of Biological Chemistry, vol. 272, p. 3406 (1997)], 3) PPARγ is expressed at high levels in activated macrophages, with the transcription of a gene involved in inflammation inhibited by the addition of a ligand therefor [Nature, vol. 391, p. 79 (1998)], and 4) PPARγ ligands suppress the production of inflammatory cytokines (TNFα, IL-1β, IL-6) by monocytes [Nature, vol. 391, p. 82 (1998)].
There is a demand for development of a novel compound useful as an agent for preventing or treating diabetes mellitus, hyperlipidemia, impaired glucose tolerance, inflammatory diseases, arteriosclerosis etc., and having pharmaceutically excellent properties such as low side effects, etc.